Precision Medicine will need to get out of the pharma silo that is based on symptoms

Welcome to the digital era of biology (and to this modest blog I started in early 2005).To cure many diseases, like cancer or cystic fibrosis, we will need to target genes (mutations, for ex.), not organs! I am convinced that the future of replacement medicine (organ transplant) is genomics (the science of the human genome). In 10 years we will be replacing (modifying) genes; not organs!

The "dead-donor rule" requires patients to be declared dead before the removal of life-sustaining organs for transplantation. The concept of brain death was developed, in part, to allow patients with devastating neurologic injury to be declared dead before the occurrence of cardiopulmonary arrest. Brain death is essential to current practices of organ retrieval because it legitimates organ removal from bodies that continue to have circulation and respiration, thereby avoiding ischemic injury to the organs.

The concept of brain death has long been recognized, however, to be plagued with serious inconsistencies and contradictions.

Indeed, the concept fails to correspond to any coherent biological or philosophical understanding of death. We review the evidence and arguments that expose these problems and present an alternative ethical framework to guide the procurement of transplantable organs. This alternative is based not on brain death and the dead-donor rule, but on the ethical principles of nonmaleficence (the duty not to harm, or primum non nocere) and respect for persons. We propose that individuals who desire to donate their organs and who are either neurologically devastated or imminently dying should be allowed to donate their organs, without first being declared dead. Advantages of this approach are that (unlike the dead-donor rule) it focuses on the most salient ethical issues at stake, and (unlike the concept of brain death) it avoids conceptual confusion and inconsistencies. Finally, we point out parallel developments, both domestically and abroad, that reflect both implicit and explicit support for our proposal.

ABSTRACT The "standard position" on organ donation is that the donor must be dead in order for vital organs to be removed, a position with which we agree. Recently, Robert Truog and Walter Robinson have argued that (1) brain death is not death, and (2) even though "brain dead" patients are not dead, it is morally acceptable to remove vital organs from those patients. We accept and defend their claim that brain death is not death,

and we argue against both the US "whole brain" criterion and the UK "brain stem" criterion. Then we answer their arguments in favour of removing vital organs from "brain dead" and other classes of comatose patients. We dispute their claim that the removal of vital organs is morally equivalent to "letting nature take its course", arguing that, unlike "allowing to die", it is the removal of vital organs that kills the patient, not his or her disease or injury. Then, we argue that removing vital organs from living patients is immoral and contrary to the nature of medical practice. Finally, we offer practical suggestions for changing public policy on organ transplantation.

"There were never sound scientific or philosophical grounds for a redefinition of death based on the loss of testable brain function while the body remains alive 1. Pressure for a viable heart for transplantation nevertheless resulted in a diagnosis of death on some such basis in Cape Town 2, in 1967. There followed “a euphoric, uncontrolled epidemic of heart transplantation around the world”3. This, together with demand for other organs which, to be viable in recipients, required that they be perfused until their removal, necessitated “the production of a set of legal and philosophical justifications”2 for procedures which would otherwise be seen as assault.

The story of how the Harvard Brain Death Committee produced, in 1968, a facilitating redefinition of death based on “irreversible coma” with “no discernible central nervous system activity” makes interesting reading4. The ease with which their novel redefinition of death became incorporated into American law, and subsequently accepted in many other countries, gave food for thought. It seemed to resist attacks upon its inconsistencies and contradictions because of its utility - indeed its perceived necessity to some transplant practices.

That is, until last year [2003]. Fittingly, the paper formally admitting that the concept of brain death - as this new form of death became widely known - “fails to correspond to any coherent biological or philosophical understanding of death” came from the Harvard Medical School too 5.

While the philosophical arguments about concepts of death may be for others, the possibility of diagnosing - with the necessary certainty - the “irreversible cessation of all functions of the entire brain, including the brain stem”, while the rest of the body remains alive, has always been the concern of the doctor. That “whole brain” definition was the requirement stipulated in the quaintly named Uniform Determination of Death Act (1981) if death were to be certified on other than the universally accepted cardiorespiratory basis. The Harvard tests - essentially of brainstem mediated reflexes and ventilator dependence, with or without EEG, in patients whose coma was believed irremediable - clearly lacked the power to make that diagnosis. The many protocols in use worldwide failed similarly. Indeed, their very number6 proclaimed the fact that the syndromes they diagnosed could not be one and the same entity7. And prominent among the variations was the apnoea test, which might lead to the misdiagnosis of respiratory centre failure if inadequately stimulating. If stringent, it might prove lethal 8.

Truog and Robinson acknowledge that many patients currently diagnosed “brain dead” do not, as a matter of fact, meet the American legal requirements governing that practice. They say that many of them retain demonstrable brain function - and that this knowledge, which should be uncomfortable to those certifying death on the basis that there is none, is set aside on the premise that it is not “significant”. That practice is reminiscent of the stance assumed by those who foisted “brain death” upon us here in the UK in 1979. They simply promulgated a set of prognostic criteria, first published in 1976, with a directive that they were to be used thenceforth as criteria for the diagnosis of death9 . The illogicality of that change of use was pointed out in 1980 10. The diagnosis (of “brain death”) was crucially dependent upon the absence of specified brainstem reflexes. Other persisting brainstem function, such as blood pressure control, was to be ignored. EEG activity was not to be sought. If demonstrated, it was to be set aside as of no “significance”. Such was the pretence to knowledge of our marvellous brain’s function which did not, and still does not, exist.

The term “brain death” was formally abandoned, in this country [the UK], in 1995 11. But comatose, ventilator-dependent patients are still being certified “dead” for transplant purposes using similar tests. These are now held to diagnose the irreversible loss of the capacity for consciousness, although no sound scientific evidence has been advanced to support that claim.

Nor, since these patients are not exposed to the anoxic drive stimulus, do they have the power to diagnose the irreversible loss of the capacity to breathe. That being so, the merits and demerits of the new conceptual basis for certifying these patients dead should be of no practical concern to the doctors who care for them.

Where requests for the organs of such patients are concerned, Truog and Robinson (like others12,13) propose the abandonment of all obfuscation about their status in the dying process. They suggest that people should be allowed to donate their organs when they become “neurologically devastated or imminently dying”, without first being declared dead. This refreshing call to face the facts has implications for the validity of the “consent” given by those led to believe that their offer of organs will not be taken up until after their death. But it may be that more will be prepared to register as prospective donors on the proposed new basis if it is fully and frankly explained - and the necessary legislation enacted after open debate."

9. Conference of Medical Royal Colleges and their Faculties in the UK. Memorandum on the diagnosisof death. BMJ 1979;I:332

10. Evans DW, Lum LC. Brain death. Lancet 1980 (November 8th):1022

11. Working Group convened by the Royal College of Physicians and endorsed by the Conference of Medical Royal Colleges and their Faculties in the United Kingdom. Criteria for the diagnosis of brain stem death. J Roy Coll Physns Lond 1995;29:381-2

Who are you?

In March 2005, I've initiated a blog about bioethics. Organ replacement technologies and genomics are part of today's sustainable health economics. This is not medicine under ideological pressure ! ...